Ear can be classified into external ear from auricle to external auditory canal, middle ear with ear drum and auditory ossicle, and internal ear with cochlear canal and auditory nerve. Since sound is acoustic energy, it can be transmitted from auricle through external auditory canal to vibrate ear drum. The vibration of ear drum is transmitted to auditory ossicle comprised of 3 small bones connected to ear drum via mechanical energy. Strapes, the distal bone of auditory ossicle is connected to cochlear canal thereby transmitting the energy to lymph in cochlear canal. Transmitted energy can induce wave in lymph by which hair cells inside of cochlear canal can be stimulated. The movement of hair cells cause ionic change thereby neurotransmitters are transferred to the auditory nerve attached to hair cells in which acoustic sound is transmitted to brain in the form of electric energy. Sound transmitting organs such as external ear and middle ear can be recovered from diseases such as inflammation by treatment or surgery in most cases, and the hearing loss therefrom can be improved after treatment as well. Such hearing loss is called conductive hearing loss. Meanwhile, hearing loss caused by cochlear canal, the organ sensing sound, auditory nerve transmitting sound via electric energy, and the brain area participating in comprehensive roles such as distinction and understanding of sound is called sensorineural hearing loss.
Among sensory organs of body, auditory organ is one of the most basic and important sense for communication enabling to learn language, acquire knowledge, take part in social activities, and enjoy human life. Since most cases of hearing loss correspond to sensorineural hearing loss without current therapeutic methods available except prevention, once occurred, utilization of assistant means such as hearing aid or implantation of mechanical devices in the body are adopted to help hearing. Sensorineural hearing loss can be classified by the origin or time of outbreak, for example, innate hearing loss and acquired hearing loss depending on the time thereof. Innate hearing loss corresponds to the damage caused before birth from genetic, fetal or embryonic problems. Most cases of innate hearing loss are extremely severe in degree and impossible to learn language without separate training or education. In most cases of innate hearing loss, hearing aid or cochlear implant (the device to stimulate auditory nerve by electric stimulus to be implanted in the body and separate external device to be worn to listen) with high output is adopted to help hearing. However, if the degree of hearing loss is severe, the effectiveness of assistant devices such as hearing aid or cochlear implant is low with huge difference from normal hearing ability, thereby lots of inconvenience in daily lives remains. In case of acquired hearing loss, it can be caused by diseases, noise, drugs or accidents after birth, with causative agents such as noise, drugs, aging, trauma, and viruses. Among these, hearing loss caused by noise and aging is appreciably increasing recently. Development of science and technology results to the extension of life span, which in turn leads to the worldwide increase of elderly population rapidly. Since most cases of senile hearing loss also correspond to sensorineural hearing loss, there is no available drug or treatment method for treating or ameliorating disease except prevention or management thereof. Recent industrialization of society also contributes to rapid increase of the population suffered from hearing loss due to noise. Not only noise-induced hearing loss related with jobs such as workers or soldiers working in noisy environment but also that related with culture and leisure activities are increasing. According to the Korean Industrial Accidents Act, exposure to environmental noise of not less than 90 dB can cause damage to auditory sense. According to Occupational Safety and Health Administration (OSHA) of U.S., noise management is under control to the environment having noise level not less than 85 dB. From studies, human auditory organ was reported to be affected by noise not less than 75 dB. Considering that the noise level not less than 75 dB corresponds to that of roadside with driving cars, everyone in the industrial society can be regarded as living under the noise harmful to auditory organs. Besides of environment noise compelled, there are many cases of teenagers' exposure to loud sound such as leisure activity using MP3. Therefore, recent noise-induced hearing loss is seen in various age groups. Noise-induced hearing loss due to MP3 utilization and the likes from young age can damage hearing so that conversation can be held only with the help of hearing aid in their 40's. The degree of hearing loss gets more severe when accompanied with physical aging. As the degree of hearing loss gets severe, the effectiveness of assistant devices such as hearing aid is lowered. High degree of hearing loss will finally cause serious problems in communication. That is, the young generation experiencing current noise-induced hearing loss will suffer more severe hearing loss in their elderly. Hearing loss plays important roles in determining the quality of lives of various generations from the old to the young.
In these days, pre-clinical studies with antioxidants, N-methyl-D-aspartate (NMDA) antagonists, inhibitors of apoptosis, growth factors and the likes had been reported to discover effective substances for preventing and treating hearing loss, but they showed limitation to be progressed to the stage of clinical studies (Prasher D., Lancet, 352, pp 1240-1242, 1998). From initial study stage, the use of antioxidant to neutralize reactive oxygen species (ROS) and reactive nitrogen species (RNS) was proven to inhibit the cell damage of cochlear from animal experiments, but said substance was not developed into drugs. N-acetyl cysteine (NAC) and methionine (MET) were reported to be useful for preventing hearing loss, and NAC, the prodrug of GSH was shown to enhance the production of GSH (Meister A., Pharmacol. Ther., 51, pp 155-194, 1991). High level of NAC showed preventive effects on noise-induced hearing loss with muco-polycarbohydrate-hydrolases for respiratory diseases wherein MET was converted into natural amino acid cysteine. Other investigators focused to inhibit apoptosis, and it was reported that GPx mimic played preventive roles in the damage of outer hair cells caused by noise. Among these studies, Mg, NAC and Ebselen showed their efficacy upto clinical stages. When 300 young soldiers were administered with 4 g of granular Mg daily and compared with control group administered with placebo at 1 week after exposure to noise, they were reported to have less degree of permanent hearing loss (Attias J. et al., Am. J. Otolaryngol., 15, pp 26-32, 1994). Administration of Mg to the soldiers exposed to lower degree of noise showed decrease in temporary hearing loss, and 600 U.S. navy soldiers administered with NAC for 2 weeks during weapons training showed decrease in permanent hearing loss. From experiments with animal model, it was reported that high level of NAC had preventive effects on noise-induced hearing loss but limited effects on permanent hearing loss (Kopke R. D. et al., Hear. Res., 149, pp 138-146, 2000; Kramer S. et al., American Academy of Audiology Annual Convention and Expo, Washington D.C., USA, Poster Presentation, pp 502, 2005). When 60 U.S. soldiers were taken Ebselen for 2 weeks during weapons training, it was reported to have effects on both temporary and permanent hearing losses (Yamasoba T. et al., Neurosci. Lett., 380, pp 234-238, 2005).
Until now, there is no approved drug for preventing and treating noise-induced hearing loss, with only academic report of preclinical studies and Mg, NAC and Ebselen drug in clinical stages.
Meanwhile, in the field of oriental medicine, it was reported that steamed Rehmannia glutinosa Libschitz var. purpurea MAKINO had been used in the past for inner ear diseases such as ear noise and hearing loss, and ethanol extract of steamed Rehmannia glutinosa Libschitz var. purpurea MAKINO inhibited lipid peroxidation and removed the activities of free radical to protect HEI-OC1 auditory cells from cisplatin-induced damage (Hyeon-Hee Yu et al., Journal of Ethnopharmacology, Volume 107, Issue 3, pp 383-388, 2006).
Under the circumstances, the present inventors searched various active substances among natural substances with high safety to prevent or treat hearing loss. Surprisingly, it was found that Cuscuta japonica Choisy extract inhibited the shift of hearing threshold induced by noise effectively, and further the extract of Rehmannia glutinosa Libschitz var. purpurea MAKINO and Cuscuta japonica Choisy showed superior effects than individual extracts, thereby completing the present invention.